This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Theory and empirical evidence have linked greater biphasic effects of alcohol to heightened vulnerability to alcohol use disorders. Biphasic effects, in terms of alcohol use, refer to the primary effects that are stimulatory and rewarding (the drinker feels more talkative and uninhibited soon after beginning to drink) but are followed by effects that are more sedating, impairing and aversive (e.g., slurred speech, limited motor coordination). The fMRI of Biphasic Alcohol Effects Study will evaluate this relationship, as well as neurogenetic mechanisms that mediate alcohol response, using powerful brain imaging and molecular-genetic techniques. This research wilsl further our understanding of brain responses to alcohol and their relationship to genetic variants that confer vulnerability. A functional magnetic resonance imaging (fMRI) experiment using arterial spin labeling to measure regional cerebral blood flow and regional brain ethanol levels will test aspects of this model. Specifically, the goals of the study are to: (1) Test a model developed by Newlin concerning brain mechanisms that may mediate the biphasic response to alcohol. Brain mechanisms that mediate the biphasic effects of alcohol will be measured using functional magnetic resonance imaging (fMRI) techniques [arterial spin labeling (ASL)] that allow assessment of regional cerebral blood flow;(2) Determine venous blood and brain pharmacokinetics of alcohol. This will allow us to expand our understanding of the relations among venous blood alcohol concentrations, regional and temporal brain ethanol levels;(3) Relate biphasic regional cerebral blood flow and brain alcohol levels to addiction vulnerability genotypes.